Complex Regional Pain SyndromeEarly Phase 1NCT02753101
[18F]FTC-146 PET/MRI in Healthy Volunteers and in CRPS and Sciatica
A Early Phase 1 study testing [18F]-FTC-146 in people with Complex Regional Pain Syndrome and Sciatica, run by Stanford University at 1 site in United States.
Trial summary
Chronic pain can result from injured or inflamed nerves, as occurs in people suffering from sciatica and CRPS. These nerve injuries or regions of nerve irritation are often the cause of pain in these conditions, but the current diagnostic tools are limited in pinpointing the area of origin. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Complex Regional Pain Syndrome, Sciatica
- What is being tested?
- [18F]-FTC-146
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Feb 2016to 16 Feb 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General:
- At least 18 years of age
- Either male or female
- Sciatica:
- History of pain shooting down a leg below the knee, to the foot or toes
- Visual analog scale (VAS) at enrollment of >4 with leg pain greater in intensity than the back pain
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- Focal disc herniation on MRI correlating with radicular symptoms defined as pain or paresthesias into the leg.
- Examination with correlating radicular signs defined as any of the following:
- pain reproduction with straight-leg-raising (pain shooting down the leg with less than 60 degrees elevation)
- radicular pattern sensory changes (such as numbness or paresthesias) in the same area as pain
- signs of radiculopathy (weakened hallux extension and/or Achilles tendon reflex)
- The above inclusion criteria can be met OR individuals who have been determined to have a very high clinical suspicion of having Sciatica as determined by the referring pain specialist can be included. This suspicion will be documented in the patient's medical record.
- CRPS:
- Disease duration of 6 months or longer
- Continuing pain, which is disproportionate to any inciting event
- Must report at least one symptom in three of the four following categories:
- Sensory: Reports of hyperesthesia and/or allodynia
- Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
- Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry
- Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
- Must display at least one sign at time of evaluation In two or more of the following categories:
- Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement)
- Vasomotor: Evidence of temperature asymmetry ( >1°C) and/or skin color changes and/or asymmetry
- Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
- Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
- There is no other diagnosis that better explains the signs and symptoms
- For research purposes, diagnostic decision rule will be at least one symptom in all four symptom categories and at least one sign (observed at evaluation) in two or more sign categories.
- The above inclusion criteria can be met OR individuals who have been determined to have a very high clinical suspicion of having CRPS as determined by the referring pain specialist can be included. This suspicion will be documented in the patient's medical record.
Who cannot join
- General:
- Another active disorder which could explain the symptoms in the opinions of the investigator
- Failure to give informed consent
- Presence of MRI-incompatible materials/devices
- Any medication that may affect pain or 18F-FTC-146 uptake or adverse drug interactions with steroids or amino amide local anesthetics (e.g. lidocaine, bupivacaine, ropivacaine)
- Pregnant or nursing
Show all 28Show fewer
- Ongoing menstrual period
- Severe comorbid conditions
- Unable to read or complete questionnaires in English
- Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study
- Sciatica:
- Any condition that may interfere with interpretation of 18F-FTC-146 uptake in the region of the pelvis, thighs or lower spine including, but not limited to,
- Spinal, hip or pelvic surgery or prosthesis
- Cancer
- Radiation therapy
- Autoimmune disorders
- Current infections
- Inability to void bladder completely, such as in prostatic enlargement
- Any urinary retention, such as in outlet obstruction, hydronephrosis etc.
- Cauda equina syndrome
- Developmental spinal deformities
- Scoliosis >20 degrees
- Spondylolysis
- Vertebral fractures
- Inflammatory spondylopathy
- Prior lumbar surgery
- CRPS:
- Presence of current or past pulmonary, hepatic, renal disease, arthritis, hematopoietic, and neurological diseases not related to CRPS.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Biodistribution and Pharmacokinetic Determination of the PET Radiopharmaceutical [18F]FTC-146 Using PET/MRI in Healthy (Asymptomatic) Volunteers and in Patients With CRPS and Sciatica
Chronic pain can result from injured or inflamed nerves, as occurs in people suffering from sciatica and CRPS. These nerve injuries or regions of nerve irritation are often the cause of pain in these conditions, but the current diagnostic tools are limited in pinpointing the area of origin. Several studies have implicated involvement of sigma-1 receptors in the generation and perpetuation of chronic pain conditions, others are investigating anti sigma-1 receptor drugs for the treatment of chronic pain. Using the sigma-1 receptor (S1R) detector and experimental radiotracer [18F]FTC-146 and positron emission tomography/magnetic resonance imaging (PET/MRI) scanner, the researchers may potentially identify the source of pain generation in patients suffering from complex regional pain syndrome (CRPS) and chronic sciatica. The ultimate goal is to assist in the optimization of pain treatment regimens using an [18F]FTC-146 PET/MRI scan.
The study is not designed to induce any physiological/pharmacological effect.
Read the detailed description
Participants are either pain free (control) or will be recruited based on established criteria for sciatica or CRPS. A signed consent will be obtained from willing participants.
For the PET/MRI scan, the participants will be injected with [18F]FTC-146 intravenously. After injection, simultaneous PET and MRI scans will be acquired using a hybrid PET/MRI scanner. Throughout scanning, participants will be monitored for blood pressure, temperature, heart rate and pulse oximetry. Participants will be asked to void their bladder as frequently as they can to reduce radiation exposure. Following the scan, participants will be contacted to check for adverse drug events, and any events will be recorded in the case report.
Evidence in the literature points strongly toward an involvement of S1 receptors in nervous system inflammation, which is known to be an important biologic disease/disorder mechanism for maintenance and perpetuation of chronic pain.
The main purpose of this research study is to image and identify activated pain pathways in human subjects using [18F]FTC-146 PET/MRI.
- Conditions
- Complex Regional Pain Syndrome, Sciatica
- Being tested
- [18F]-FTC-146
- Keywords
- Positron Emission Tomography, Magnetic Resonance Imaging, PET/MRI, sigma-1 receptor, radiopharmaceutical, complex regional pain syndrome, sciatica, chronic pain
- Medical subject headings
- Complex Regional Pain Syndromes, Sciatica, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]-FTC-146Drug
Also called Sigma-1 receptor radioligand
10 mCi± 1 mCi of [18F]FTC-146 intravenously
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | [18F]-FTC-146 Receives: Drug: [18F]-FTC-146 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biodistribution of [18F]FTC-146
Biodistribution of [18F]FTC-146 will be analyzed by drawing regions of interest (ROI) for the reported organs on the PET/MRI images. Processing software will quantify the amount of [18F]FTC-146 uptake within the ROI's and display the amount in terms of standardized uptake values (SUV's).
Biodistribution data will be obtained by drawing regions of interest (ROI's) around organs on the PET/MRI images. Processing software will quantify the amount of [18F]FTC-146 uptake within the ROI's and display the amount in terms of standardized uptake values (SUV's).
Pharmacokinetic data will be calculated using kinetic analysis (mathematical modeling) of [18F]FTC-146 clearance from the blood.
Measured: an estimated average of 2 hours
Secondary outcomes (2)
Dosimetry of [18F]FTC-146
Dosimetry calculations will be determined using the biodistribution (reported as a primary outcome measure) and pharmacokinetics of the tracer in human organs.
Measured: an estimated average of 2 hours
Incidence of Adverse Events
[18F]FTC-146 Single IV Treatment-Emergent Adverse Events will be established by collectively assessing real-time vitals monitoring during scans, serial clinical lab work (i.e. blood tests), and patient symptomatic report at baseline and up to 7 days post-injection.
Measured: Baseline and up to 7 days after tracer injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2016 (estimated)
- Study start9 Feb 2016
- Primary completion9 Feb 2017
- Study completion16 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Complex Regional Pain SyndromeStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Mississippi Medical Center
- Responsible party
- Principal investigator, Sandip Biswal, Stanford University
- Investigators
- Sandip Biswal, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02753101
- Sponsor's protocol ID
- 32231
- Status last verified
- Mar 2018
- First submitted
- 22 Apr 2016
- Last updated
- 5 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
James ML, Shen B, Nielsen CH, Behera D, Buckmaster CL, Mesangeau C, Zavaleta C, Vuppala PK, Jamalapuram S, Avery BA, Lyons DM, McCurdy CR, Biswal S, Gambhir SS, Chin FT. Evaluation of sigma-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET. J Nucl Med. 2014 Jan;55(1):147-53. doi: 10.2967/jnumed.113.120261. Epub 2013 Dec 12.
PubMed 24337599James ML, Shen B, Zavaleta CL, Nielsen CH, Mesangeau C, Vuppala PK, Chan C, Avery BA, Fishback JA, Matsumoto RR, Gambhir SS, McCurdy CR, Chin FT. New positron emission tomography (PET) radioligand for imaging sigma-1 receptors in living subjects. J Med Chem. 2012 Oct 11;55(19):8272-8282. doi: 10.1021/jm300371c. Epub 2012 Sep 20.
PubMed 22853801Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, Coleman RE, Wahl R, Paschold JC, Avril N, Einhorn LH, Suh WW, Samson D, Delbeke D, Gorman M, Shields AF. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008 Mar;49(3):480-508. doi: 10.2967/jnumed.107.047787. Epub 2008 Feb 20.
PubMed 18287273Puente B, Nadal X, Portillo-Salido E, Sanchez-Arroyos R, Ovalle S, Palacios G, Muro A, Romero L, Entrena JM, Baeyens JM, Lopez-Garcia JA, Maldonado R, Zamanillo D, Vela JM. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain. 2009 Oct;145(3):294-303. doi: 10.1016/j.pain.2009.05.013. Epub 2009 Jun 7.
PubMed 19505761Entrena JM, Cobos EJ, Nieto FR, Cendan CM, Gris G, Del Pozo E, Zamanillo D, Baeyens JM. Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice. Pain. 2009 Jun;143(3):252-261. doi: 10.1016/j.pain.2009.03.011. Epub 2009 Apr 17.
PubMed 19375855Maurer AH. Combined imaging modalities: PET/CT and SPECT/CT. Health Phys. 2008 Nov;95(5):571-6. doi: 10.1097/01.HP.0000334064.46217.20.
PubMed 18849691
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biodistribution and Pharmacokinetic Determination of the PET Radiopharmaceutical [18F]FTC-146 Using PET/MRI in Healthy (Asymptomatic) Volunteers and in Patients With CRPS and Sciatica
- ClinicalTrials.gov ID
- NCT02753101
- Acronym / sponsor ID
- 32231
- Conditions
- Complex Regional Pain Syndrome, Sciatica
- Keywords
- Positron Emission Tomography, Magnetic Resonance Imaging, PET/MRI, sigma-1 receptor, radiopharmaceutical, complex regional pain syndrome, sciatica, chronic pain
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- University of Mississippi Medical Center
- Study start
- 9 Feb 2016 (actual)
- Primary completion
- 9 Feb 2017 (actual)
- Study completion
- 16 Feb 2017 (actual)
- First posted
- 27 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic pain can result from injured or inflamed nerves, as occurs in people suffering from sciatica and CRPS. These nerve injuries or regions of nerve irritation are often the cause of pain in these conditions, but the current diagnostic tools are limited in pinpointing the area of origin. Several studies have implicated involvement of sigma-1 receptors in the generation and perpetuation of chronic pain conditions, others are investigating anti sigma-1 receptor drugs for the treatment of chronic pain. Using the sigma-1 receptor (S1R) detector and experimental radiotracer [18F]FTC-146 and positron emission tomography/magnetic resonance imaging (PET/MRI) scanner, the researchers may potentially identify the source of pain generation in patients suffering from complex regional pain syndrome (CRPS) and chronic sciatica. The ultimate goal is to assist in the optimization of pain treatment regimens using an [18F]FTC-146 PET/MRI scan.
The study is not designed to induce any physiological/pharmacological effect.
Detailed description
Participants are either pain free (control) or will be recruited based on established criteria for sciatica or CRPS. A signed consent will be obtained from willing participants.
For the PET/MRI scan, the participants will be injected with [18F]FTC-146 intravenously. After injection, simultaneous PET and MRI scans will be acquired using a hybrid PET/MRI scanner. Throughout scanning, participants will be monitored for blood pressure, temperature, heart rate and pulse oximetry. Participants will be asked to void their bladder as frequently as they can to reduce radiation exposure. Following the scan, participants will be contacted to check for adverse drug events, and any events will be recorded in the case report.
Evidence in the literature points strongly toward an involvement of S1 receptors in nervous system inflammation, which is known to be an important biologic disease/disorder mechanism for maintenance and perpetuation of chronic pain.
The main purpose of this research study is to image and identify activated pain pathways in human subjects using [18F]FTC-146 PET/MRI.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: [18F]-FTC-146[18F]-FTC-146 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- At least 18 years of age
- Either male or female
- History of pain shooting down a leg below the knee, to the foot or toes
- Visual analog scale (VAS) at enrollment of >4 with leg pain greater in intensity than the back pain
- Focal disc herniation on MRI correlating with radicular symptoms defined as pain or paresthesias into the leg.
Key exclusion criteria (28 listed)
- Another active disorder which could explain the symptoms in the opinions of the investigator
- Failure to give informed consent
- Presence of MRI-incompatible materials/devices
- Any medication that may affect pain or 18F-FTC-146 uptake or adverse drug interactions with steroids or amino amide local anesthetics (e.g. lidocaine, bupivacaine, ropivacaine)
- Pregnant or nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]-FTC-146Also: Sigma-1 receptor radioligand10 mCi± 1 mCi of [18F]FTC-146 intravenously | Drug | Single Arm |
Primary outcome
Biodistribution of [18F]FTC-146
Time frame: an estimated average of 2 hours
Biodistribution of [18F]FTC-146 will be analyzed by drawing regions of interest (ROI) for the reported organs on the PET/MRI images. Processing software will quantify the amount of [18F]FTC-146 uptake within the ROI's and display the amount in terms of standardized uptake values (SUV's). Biodistribution data will be obtained by drawing regions of interest (ROI's) around organs on the PET/MRI images. Processing software will quantify the amount of [18F]FTC-146 uptake within the ROI's and display the amount in terms of standardized uptake values (SUV's). Pharmacokinetic data will be calculated using kinetic analysis (mathematical modeling) of [18F]FTC-146 clearance from the blood.
2 secondary outcomes
Dosimetry of [18F]FTC-146
Time frame: an estimated average of 2 hours
Incidence of Adverse Events
Time frame: Baseline and up to 7 days after tracer injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2018.
- Background: PubMed 24337599James ML, Shen B, Nielsen CH, Behera D, Buckmaster CL, Mesangeau C, Zavaleta C, Vuppala PK, Jamalapuram S, Avery BA, Lyons DM, McCurdy CR, Biswal S, Gambhir SS, Chin FT. Evaluation of sigma-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET. J Nucl Med. 2014 Jan;55(1):147-53. doi: 10.2967/jnumed.113.120261. Epub 2013 Dec 12.
- Background: PubMed 22853801James ML, Shen B, Zavaleta CL, Nielsen CH, Mesangeau C, Vuppala PK, Chan C, Avery BA, Fishback JA, Matsumoto RR, Gambhir SS, McCurdy CR, Chin FT. New positron emission tomography (PET) radioligand for imaging sigma-1 receptors in living subjects. J Med Chem. 2012 Oct 11;55(19):8272-8282. doi: 10.1021/jm300371c. Epub 2012 Sep 20.
- Background: PubMed 18287273Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, Coleman RE, Wahl R, Paschold JC, Avril N, Einhorn LH, Suh WW, Samson D, Delbeke D, Gorman M, Shields AF. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008 Mar;49(3):480-508. doi: 10.2967/jnumed.107.047787. Epub 2008 Feb 20.
- Background: PubMed 19505761Puente B, Nadal X, Portillo-Salido E, Sanchez-Arroyos R, Ovalle S, Palacios G, Muro A, Romero L, Entrena JM, Baeyens JM, Lopez-Garcia JA, Maldonado R, Zamanillo D, Vela JM. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain. 2009 Oct;145(3):294-303. doi: 10.1016/j.pain.2009.05.013. Epub 2009 Jun 7.
- Background: PubMed 19375855Entrena JM, Cobos EJ, Nieto FR, Cendan CM, Gris G, Del Pozo E, Zamanillo D, Baeyens JM. Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice. Pain. 2009 Jun;143(3):252-261. doi: 10.1016/j.pain.2009.03.011. Epub 2009 Apr 17.
- Background: PubMed 18849691Maurer AH. Combined imaging modalities: PET/CT and SPECT/CT. Health Phys. 2008 Nov;95(5):571-6. doi: 10.1097/01.HP.0000334064.46217.20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandip Biswal, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [18F]-FTC-146 in people with Complex Regional Pain Syndrome and Sciatica, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biodistribution of [18F]FTC-146 (time frame: an estimated average of 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02753101, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2018.